Animal neurotoxins have proven to be of significant value as specific affinity ligands in research on excitable membrane function and structure. Recent electrophysiological experiments have demonstrated that a neurotoxin contained in venom from the scorpion Pandinus emperator selectively alters the activation kinetics of delayed rectifier potassium channels in frog myelinated nerve and skeletal muscle. A partially purified neurotoxin has been successfully radiolabeled and shown to bind in a saturable fashion to putative potassium channel components solubilized from appropriate sources of excitable membrane. Taken together, these initial experiments support the idea that Pandinus neurotoxin will provide a useful affinity ligand for studies on voltage dependent potassium channels. The electrophysiological experiments proposed here will provide a complete characterization of the activity of this toxin using voltage clamp experiments on frog myelinated nerve and squid giant axon. This will be complemented by a biochemical characterization of the neurotoxin and a determination of the kinetics, affinity and voltage dependence of toxin binding to excitable membranes. Initial experiments directed toward the solubilization of the Pandinus toxin binding components will be completed and extended. This proposal outlines a body of work requisite to the application of this unique neurotoxin to studies on the, number, distribution, regulation, turnover, and structure of delayed rectifier potassium channels in a variety of normal and pathological tissues.